Researchers have discovered that a key genetic switch in the liver regulates glucose metabolism and insulin action in other organs of the body and continue to investigate how this impacts diabetes.

Researchers from Helmholtz Zentrum München, in collaboration with colleagues of the Heidelberg University Hospital, Technische Universität München and the Medical Faculty of the University of Leipzig, have discovered a new mechanism that is responsible for the regulation of glucose metabolism.

A team led by the metabolism expert Prof. Stephan Herzig, director of the Institute for Diabetes and Cancer at Helmholtz Zentrum München (IDC), has discovered that the transforming growth factor beta 1-stimulated clone 22 D4, abbreviated TSC22D4, acts as a molecular switch in the liner and from there regulates genes that can influence the metabolism throughout the body.

“The current study is a successful continuation of our research activities with colleagues from the Internal Medicine at Heidelberg University Hospital,” Herzig said in a statement.

Researchers were able to observe that increased production of TSC22D4 in the liver of mice with cancer lead to severe weight loss in 2013 and in the current study they investigated the role of this gene regulator in connection with diabetes.

Diabetes mellitus is a chronic disease characterized by a disruption of the glucose metabolism and impaired response of the body to the hormone insulin that has become increasingly prevalent in the population with more than 6 million people affected in Germany alone.

The researchers showed in diabetic mice that inactivation of TSC22D4 led to an improvement of the insulin action and glucose metabolism and after further analysis TSC22D4 showed to inhibit the production of the lipcalin13 protein, which is released as a messenger substance from the liver and can regulate the glucose metabolism in other organs.

They also examined liver tissue specimens of 66 patients with and without type 2 diabetes and found that in the liver of the diabetes patients compared to people with normal glucose metabolism, the TSC22D4 gene was expressed significantly more often and lipcalin13 was produced correspondingly less often.

“The strong influence of TSC22D4 on the metabolism in tumor diseases suggested that it could also play a role in metabolic diseases,” first author Bilgen Ekim Üstünel, Ph.D., of the IDC, said in a statement.

Herzig explained what will happen next regarding the study.

“For the treatment of diabetes there is only a very limited number of therapeutic targets,” he said. “Next, we want to investigate whether our findings can lead to the development of a new therapeutic approach to treat diabetes and insulin resistance.”  

The study appears in Nature Communications.